Is the "Summer of Love" Over? Positive Publication Bias Plagues Pharmaceutical Research

Evidence-based practice is only as good as the available “evidence”–and on this subject, research points to a continuing problem with both the methodology and type of studies that make it into the professional literature. Last week, PloS Medicine, a peer-reviewed, open access journal of the Public Library of Science, published a study showing a positive publication bias in research on so-called atypical antipsychotic drugs. In comparing articles appearing in journals to the FDA database, researchers found that almost all postive studies were published while clinical trials with negative or questionable results were not or–and get this–were published as having positive results!

Not long ago, similar yet stronger results appeared in the same journal on anti-depressants. Again, in a comparison with the FDA registry, researchers found all postive studies were published while clinical trials with negative or questionable results were not or–and get this–were published as having positive results! The problem is far from insignificant. Indeed, a staggering 46% of studies with negative results were not published or published but reported as positive.

Maybe the “summer of love” is finally over for the field and broader American public. Today’s Chicago Tribune has a story by Kate Kelland and Ben Hirschler reporting data about sagging sales of anti-depressants and multiple failures to bring new, “more effective” drug therapies to market. Taken together, robust placebo effects, the FDA mandate to list all trials (positive and negative), and an emphasis in research on conducting fair comparisons (e.g., comparing any new “products” to existing ones) make claims about “new and improved” effectiveness challenging.

Still one sees ads on TV making claims about the biological basis of depression–the so called, “biochemical imbalance.” Perhaps this explains why a recent study of Medicaid clients found that costs of treating depression rose by 30% over the last decade while the outcomes did not improve at all during the same period. The cause for the rise in costs? Increased use of psychiatric drugs–in particular, anti-psychotics in cases of depression.

“It’s a great time for brain science, but at the same time a poor time for drug discovery for brain disorders,” says David Nutt, professor of neuropsychopharmacology, cited in the Chicago Tribune, “That’s an amazing paradox which we need to do something about.”

Here’s an idea: how about not assuming that problems in living are reduceable to brain chemistry? That the direction of causality for much of what ails people is not brain to behavior but perhaps behavior to brain? On this note, it is sad to note that while the percentage of clients prescribed drugs rose from 81 to 87%–with no improvement in effect–the number of those receiving psychotherapy dropped from 57 to 38%.

Here’s what we know about psychotherapy: it works and it has a far less troublesome side effect profile than psychotropic drugs. No warnings needed for dry mouth, dizziness, blood and liver problems, or sexual dysfunction. The time has come to get over the collective 1960’s delusion of better living through chemistry.